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关键词： antioxidant   gestational diabetes mellitus   oxidative stress   preeclampsia   preterm birth   reproductive toxicity  

摘要： Objective A homeostatic balance between reactive oxygen species production and the antioxidant redox system is an important component of normal pregnancy. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) preserves cellular homeostasis by enhancing the cell's innate antioxidant status to reduce oxidative stress and inflammatory damage to the cell during pregnancy. Active Nrf2, in the nucleus of the cell, transactivates various antioxidant genes. The objective of this systematic review was to synthesize evidence on the role of Nrf2 in various adverse pregnancy outcomes (APOs). Methods We conducted a systematic review of the role of Nrf2 in pregnancy. Articles written in English, Portuguese, and Spanish were obtained from three different databases from inception until January 2021. The titles, abstracts and full text were reviewed independently by six reviewers. The quality of the included studies was assessed using a quality assessment tool developed to assess basic science and clinical studies. Nrf2 expression (gene and protein), functional contributions, and association with APOs were assessed. Results A total of 747 citations were identified;80 were retained for full review. Most studies on Nrf2 have been carried out using placental tissues and placenta-derived cells. Limited studies have been conducted using fetal membranes, uterus, and cervix. Nuclear translocation of Nrf2 results in transactivation of antioxidant enzymes, including glutathione peroxidase, hemeoxygenase-1, and superoxide dismutase in gestational cells during pregnancy. This antioxidant response maintains cellular homeostasis during pregnancy. This promotes trophoblast cell survival and prevents cell death and abnormal angiogenesis in the placenta. Excessive and insufficient Nrf2 response may promote oxidative and reductive stress, respectively. This Nrf2 dysregulation has been associated with APOs including gestational diabetes mellitus, intrauterine growth restriction, reproductive toxicity, p

关键词： Screening   Esophageal   Protocol   Diagnostic accuracy   Deglutition   Deglutition disorders  

摘要： Oropharyngeal and esophageal dysphagia may occur simultaneously. However, symptoms are often evaluated separately. Few standardized, multi-texture esophageal screening protocols exist as an addition to the modified barium swallow study (MBSS). Given the gap in MBSS evaluation standards, providers may be lacking information needed to fully assess the swallowing process and create appropriate dysphagia management plans. The aim was to assess the diagnostic accuracy of a standardized esophageal screening protocol performed by an SLP compared to formal reference esophageal examinations. A cross-sectional analytic study was performed. Consecutively referred patients who underwent same-day consultation with the SLP and a gastroenterologist were included. MBSS with a standardized esophageal screen was performed. Same-day formal esophageal testing was completed and included timed barium emptying study or high-resolution manometry. Summary diagnostic accuracy measures were calculated. Seventy-three patients matched the inclusion criteria. Median age was 62.5 years (25-87), 55% were female. Sensitivity of the esophageal screen for the detection of esophageal abnormality was 83.7% (95% CI 70-91.9%);specificity was 73.7% (95% CI 55.6-85.8%). The positive likelihood ratio was 3.14 (95% CI 1.71-5.77), whereas the negative likelihood ratio was 0.22 (95% CI 0.11-0.45). Positive and negative predictive values were 82% and 76%, respectively. Use of a systematic, multi-texture esophageal screen protocol interpreted by SLPs accurately identifies multiphase dysphagia and should be considered in addition to standard MBSS testing. Inclusion of a cursory esophageal view may more adequately assess dysphagia symptoms and help to promote multidisciplinary care.

关键词： Fractional flow reserve   Myocardial   Computed tomography angiography   Coronary artery disease   Running  

摘要： Objectives To evaluate computed tomography fractional flow reserve (FFRCT) values in distal parts of the coronaries in an asymptomatic cohort of marathon runners without any coronary stenosis for potentially false-positive values. Methods Ninety-eight asymptomatic male marathon runners (age 53 +/- 7 years) were enrolled in a prospective monocentric study and underwent coronary computed tomography angiography (CCTA). CCTA data were analyzed for visual coronary artery stenosis. FFRCT was evaluated in 59 participants without coronary artery stenosis in proximal, mid, and distal coronary sections using an on-site software prototype. Results In participants without coronary artery stenosis, abnormal FFRCT values <= 0.8 in distal segments were found in 22 participants (37%);in 19 participants in the LAD;in 5 participants in the LCX;and in 4 participants in the RCA. Vessel diameters in participants with FFRCT values > 0.80 compared to <= 0.80 were 1.6 +/- 0.3 mm versus 1.5 +/- 0.3 mm for distal LAD (p = 0.025), 1.8 +/- 0.3 mm versus 1.6 +/- 0.5 mm for distal LCX (p = 0.183), and 2.0 +/- 0.4 mm versus 1.5 +/- 0.2 mm for distal RCA (p < 0.001). Conclusions Abnormal FFRCT values of <= 0.8 frequently occurred in distal coronary segments in subjects without any anatomical coronary artery stenosis. This effect is only to some degree explainable by small distal vessel diameters. Therefore, the validity of hemodynamic relevance evaluation using FFRCT in distal coronary artery segment stenosis is reduced.

关键词： adolescent   eating behaviors   metabolic and bariatric surgery   severe obesity  

摘要： Objectives: Little is known about the behavioral and psychosocial correlates of pediatric nonalcoholic fatty liver disease (NAFLD). Given diet contributes to the development and persistence of NAFLD, we examined (1) the prevalence of unhealthy eating behaviors (UEB), (2) whether these varied by NAFLD or nonalcoholic steatohepatitis (NASH) presence, and explored (3) the association of psychopathology with NAFLD. Methods: Before metabolic and bariatric surgery (MBS), adolescents (N = 159;M-age = 16.4;M-BMI = 53.7 kg/m(2), 73% girls, 62.3% white) self-reported presence/absence of 10 UEB (Questionnaire on Eating and Weight Patterns-Revised, Night Eating Questionnaire, Look AHEAD). NAFLD and NASH presence was assessed by intraoperative liver biopsy. Height/weight, blood pressure, and blood specimens were obtained. A medical comorbidity index was created (prediabetes/diabetes, dyslipidemia, elevated blood pressure). Psychopathology was assessed in a subgroup completing the Youth Self-Report (N = 98). Results: Binge eating disorder symptomatology was associated with higher odds of NAFLD whereas frequent eating out was associated with lower odds of NAFLD. Among those with NAFLD frequent eating out was associated with higher odds of NASH while nocturnal eating was associated with lower odds of NASH. Separate models identified internalizing psychopathology as associated with higher odds of NAFLD after controlling for demographics, number of UEB, and medical comorbidities. Conclusions: Results suggest potential phenotypical differences between adolescents presenting for MBS with/without NAFLD, with implications for behavioral/psychosocial targets for screening and intervention. Replication should occur in a sample with greater gender and ethnic diversity to improve generalizability. Understanding differences in the context of surgical weight loss and comorbidity resolution is indicated.

关键词： Surgical Oncology   Oncology   Surgery  

摘要： Purpose Risk stratification to select appropriate candidates for adjuvant therapy is required for esophageal cancer patients based on adjuvant therapy advancement including immunotherapy. The current study aims to develop a novel staging system using pathological stage (pStage) and response to neoadjuvant chemotherapy (NAC) for esophageal squamous cell carcinoma (ESCC). Methods ESCC patients who received NAC and underwent transthoracic esophagectomy at two Japanese high-volume esophageal centers were retrospectively reviewed. The prognostic value of NAC response was evaluated within the same pStage, and a novel risk stratification to predict cancer-specific survival (CSS) was developed. Results The HR (95% CI) of pathological responders in pStage 0-I, II, III, and IV was 0.29 (0.07-1.17), 0.37 (0.12-1.10), 0.37 (0.15-0.92), and 0.24 (0.06-0.98), respectively. Responders in pStage 0-II were classified to be in the same class and those in pStage III/IV in another group, because the 5-year CSS (5y-CSS) rate of responders in pStage 0-I, II, III, and IV was 94%, 92%, 76%, and 71%, respectively. Combining nonresponders in pStage 0-II as the same group, all patients were subdivided into five groups. Intriguingly, the 5y-CSS in pStage III-IV responders was 75%, almost identical to that of nonresponders in pStage 0-II (78%). Conclusions The histological response influenced the long-term outcomes of patients who underwent esophagectomy after NAC, even within groups stratified by pathologic stage. The current risk stratification system will contribute to selecting appropriate candidates for adjuvant therapy.

关键词： Low-risk   Papillary thyroid carcinoma   Extent of surgery   Total thyroidectomy   Thyroid lobectomy  

摘要： Purpose Recent clinical practice guidelines consider thyroid lobectomy a viable alternative for low-risk papillary thyroid carcinoma PTC measuring 1-4 cm in size. We aimed to assess the likelihood of finding postoperatively determined high-risk histopathologic features that would lead to the recommendation of completion thyroidectomy. Methods A retrospective review of patients who underwent total thyroidectomy for PTC measuring 1-4 cm in size between Jan 2012 and Jan 2018 was conducted. Patients with pre-operative high-risk characteristics were excluded: history of radiation exposure, positive family history, clinically suspicious cervical lymphadenopathy, and gross extrathyroidal extension (ETE). A hypothetical group of 245 patients remained eligible for lobectomy. The pathology specimens from the cancer-containing lobes were evaluated for high-risk features: aggressive histology, capsular and/or vascular invasion, microscopic ETE, and multifocality. A subgroup analysis was performed with 2 cm being the cut-off size. Results The average age was 39 years with 73% being females. Mean cancer size was 16 mm. Evaluation of the cancer-containing lobe for high-risk features revealed: aggressive histology (33%), ETE (12%), capsular invasion (33%), vascular invasion (17%), and ipsilateral multifocality (30%). The cumulative risk of having >= 1 high-risk feature mandating completion thyroidectomy was 59%. The risk was considerably higher for lesions <= 2 cm compared to larger lesions (64% vs.48%;p = 0.049;RR = 1.3). Conclusions A considerable proportion of patients initially eligible for lobectomy have high-risk features that only become evident at pathology. Therefore, a comprehensive approach is advocated to determine the extent of surgery for PTC incorporating patient preferences regarding risks and benefits.

关键词： Melanin   Depigmentation   Ascorbic acid   Intramucosal   Gel  

摘要： Objective Vitamin C/Ascorbic acid inhibits tyrosinase enzyme causing melanin biosynthesis suppression. This study aimed to compare the efficacy of intra-mucosal injection (mesotherapy) with topical gel as non-surgical methods for managing gingival hyperpigmentation. Materials and methods Twenty healthy non-smokers with mild to severe hyperpigmented gingiva were randomly assigned for Mesotherapy (G1);intra-mucosal injection of ascorbic acid (1/week/3 weeks);or Gel (G2), topical ascorbic acid gel (1/day/3 months). Pigmentation index (DOPI), patient satisfaction, as well as histological analysis for Fontana-Masson-stained specimens were performed at baseline and after 6 months. Comparison between groups and changes by time were analyzed using Mann-Whitney and Friedman's tests, respectively. Results The median DOPI significantly decreased after 1 month in G1 (P value < 0.001, r = 0.9) compared with non-significant change in G2. No pain experienced during or after treatment in both groups. G1 patients showed significantly higher satisfaction with treatment than G2. Mean area fraction of melanin forming cells was significantly reduced in both groups after 6 months, but the effect size was higher in G1 (r = 0.886) than in G2 (r = 0.797). Conclusions Vitamin C mesotherapy showed better and early effect than topical gel, and both techniques were not painful and esthetically satisfying in managing gingival hyperpigmentation.

关键词： EGFR   KRAS   PD-L1   skin metastases   TTF-1  

摘要： Aims Little is known regarding the histopathological and molecular features of lung adenocarcinoma skin metastases. Our study is the largest, to our knowledge, to comprehensively explore these to date. Methods and results We performed a retrospective cohort study analysing 42 lung adenocarcinoma skin metastasis samples obtained from a database of 2659 lung adenocarcinomas collected between 2010 and 2020. EGFR exon 19 deletion was detected in one patient and KRAS mutations were detected in 12 (33.3%) patients. The programmed cell death ligand 1 (PD-L1) tumour proportion score was <1% in 27 patients, >= 1% and <50% in eight patients, >= 50% in six patients and not assessable in one patient. We showed that the predominant histopathological subtype is different from that at other metastatic sites (P = 0.024). Thyroid transcription factor I (TTF-1) was more often negative in skin metastases compared to other sites (P < 0.001). The EGFR mutation rate tended to be lower for skin metastases compared to other sites (P = 0.079). Skin metastases were associated with a high rate of PD-L1-negative cases (P = 0.022). Conclusion Our work shows that the skin metastases of lung adenocarcinoma have a specific histopathological profile.

关键词： apoptosis   Lepidium draba L   male fertility   oxymetholone   sperm parameters  

摘要： This study was aimed to investigate the protective effects of Lepidium draba L. (L. draba) extract on oxymetholone (OM)-induced testicular injury in rat. Six groups of n = 5 adult male rats were used as;1: control, 2: OM (5 mg/kg OM orally), 3, 4 and 5: L. draba extract (100, 200 and 400 mg kg(-1) day(-1)) +OM (5 mg kg(-1) day(-1) OM) and 6:400 mg/kg/d L. draba extract for 30 days. Serum testosterone (T), follicle-stimulating hormone (FSH) and luteinising hormone (LH), inflammatory cytokines (IL-6, IL-10, TNF-alpha, IL-1 beta), oxidative stress (OS) indicators [superoxide dismutase, catalase, glutathione peroxidase and nitric oxide (NO)], apoptotic related genes (Bcl-2, p53, caspase-3 (c3) and Bax) were investigated. OM significantly increased the serum levels of T, proinflammatory cytokines and pro-apoptotic genes expression. Also, it decreased LH and FSH, sperm viability, count and motility. L. draba extract especially could markedly normalise the serum levels of LH and FSH, and T, restore serum antioxidant enzymes and suppressed the pro-inflammatory cytokines. Also, germ cells apoptosis was inhibited against via downregulating the p53, c3, Bax and upregulating Bcl-2. It concluded that L. draba extract could protect the function and structure of testis against OM-induced testicular toxicity via its antioxidant and anti-inflammatory properties.

关键词： Hepatocellular carcinoma   Cholangiocarcinoma   Diagnosis   Liver cancer   Magnetic resonance imaging  

摘要： Objectives To explain the new changes in pathologic diagnoses of biphenotypic primary liver cancer (PLC) according to the updated 2019 World Health Organization (WHO) classification and how it impacts Liver Imaging Reporting and Data System (LI-RADS) classification using gadoxetic acid-enhanced MRI (Gd-EOB-MRI). Methods We retrospectively included 209 patients with pathologically proven biphenotypic PLCs according to the 2010 WHO classification who had undergone preoperative Gd-EOB-MRI between January 2009 and December 2018. Imaging analysis including LI-RADS classification and pathologic review including the proportion of tumor components were performed. Frequencies of each diagnosis and subtype according to the 2010 and 2019 WHO classifications were compared, and changes in LI-RADS classification were evaluated. Univariable and multivariable analysis were performed to determine significant tumor component for LI-RADS classification. Results Of the 209 biphenotypic PLCs of the 2010 WHO classification, 177 (84.7%) were diagnosed as bipheonotypic PLCs, 25 (12.0%) as hepatocellular carcinomas (HCCs), and 7 (3.3%) as cholangiocarcinomas (CCAs) using the 2019 WHO classification. Of the 177 biphenotypic PLCs, LR-M, LR-4, and LR-5 were assigned in 77 (43.5%), 21 (11.9%), and 63 (35.5%), respectively. There were no significant differences in the proportion of LR-5 and LR-M categories between the WHO 2010 and 2019 classifications (p = 0.941). Proportion of HCC component was the only independent factor for LI-RADS classification (adjusted odds ratio, 1.02;p < 0.001). Conclusion According to the 2019 WHO classification, 15% of biphenotypic PLCs from the 2010 WHO classification were re-diagnosed as HCCs or CCAs, and a substantial proportion of biphenotypic PLCs of the 2019 WHO classification could be categorized as LR-4 or LR-5 on Gd-EOB-MRI.